Development of a fully synthetic stereoselective route to 6-deoxyerythronolide B by reiterative applications of the Lewis acid catalyzed diene aldehyde cyclocondensation reaction: a remarkable instance of diastereofacial selectivity

Myles, David C.; Schulte, Gayle K.

doi:10.1021/jo00292a045

Cited by 62 publications

(16 citation statements)

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“…One biologically relevant compound that is rich in alcohol groups is erythromycin A ( 13 ), which was first discovered and marketed as an antibiotic in the 1950s. , However, given the widespread epidemic of drug-resistance, especially toward macrolide compounds such as erythromycin, novel compounds that can combat super bacteria are required. , As such, numerous total syntheses have been reported for erythromycin and relevant derivatives. ,− While these approaches allow for the derivatization of erythromycin’s structure at various stages, the syntheses of these macrolides can be challenging given their stereochemical complexity. The direct site-selective modification of erythromycin is hence particularly attractive, as the ability to target various locations on 13 would allow for the facile and expedient synthesis of numerous derivatives for structure–activity relationship (SAR) studies.…”

Section: Group Transfer To Hydroxyl Groupsmentioning

confidence: 99%

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

2017

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The application of small molecules as catalysts for the diversification of natural product scaffolds is reviewed. Specifically, principles that relate to the selectivity challenges intrinsic to complex molecular scaffolds are summarized. The synthesis of analogs of natural products by this approach is then described as a quintessential “late-stage functionalization” exercise wherein natural products serve as the lead scaffolds. Given the historical application of enzymatic catalysts to the site-selective alteration of complex molecules, the focus of this review is on the recent studies of non-enzymatic catalysts. Reactions involving hydroxyl group derivatization with a variety of electrophilic reagents are discussed. C–H bond functionalizations that lead to oxidations, aminations, and halogenations are also presented. Several examples of site-selective olefin functionalizations and C–C bond formations are also included. Numerous classes of natural products have been subjected to these studies of site-selective alteration including polyketides, glycopeptides, terpenoids, macrolides, alkaloids, carbohydrates and others. What emerges is a platform for chemical remodeling of naturally occurring scaffolds that targets virtually all known chemical functionalities and microenvironments. However, challenges for the design of very broad classes of catalysts, with even broader selectivity demands (e.g., stereoselectivity, functional group selectivity, and site-selectivity) persist. Yet, a significant spectrum of powerful, catalytic alterations of complex natural products now exists such that expansion of scope seems inevitable. Several instances of biological activity assays of remodeled natural product derivatives are also presented. These reports may foreshadow further interdisciplinary impacts for catalytic remodeling of natural products, including contributions to SAR development, mode of action studies, and eventually medicinal chemistry.

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Section: Group Transfer To Hydroxyl Groupsmentioning

confidence: 99%

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

2017

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“…Chiral pyranoid moieties may also serve as potential templates in acylic stereochontrol. Danishefsky and co-workers devised a synthesis of (±)-6-deoxyerythronolide ( 107 , Figure 13A ) featured by reiterative application of Lewis acid catalyzed cycloaddition of diene and aldehyde to stereoselectively generate trans -disubstituted dihydropyrone (Myles and Danishefsky, 1990 ). Danishefsky diene 101 and other dimethylated diene analogs equipped with exploitable functionality can be viewed as versatile dipropionyl building blocks.…”

Section: Polypropionatesmentioning

confidence: 99%

“… (A) Synthesis of rac -6-deoxyerythronolide B (Myles and Danishefsky, 1990 ); (B) Synthesis of erythronolide A (Bode et al, 2001 ). …”

Section: Polypropionatesmentioning

confidence: 99%

Bioinspired iterative synthesis of polyketides

2015

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Diverse array of biopolymers and second metabolites (particularly polyketide natural products) has been manufactured in nature through an enzymatic iterative assembly of simple building blocks. Inspired by this strategy, molecules with inherent modularity can be efficiently synthesized by repeated succession of similar reaction sequences. This privileged strategy has been widely adopted in synthetic supramolecular chemistry. Its value also has been reorganized in natural product synthesis. A brief overview of this approach is given with a particular emphasis on the total synthesis of polyol-embedded polyketides, a class of vastly diverse structures and biologically significant natural products. This viewpoint also illustrates the limits of known individual modules in terms of diastereoselectivity and enantioselectivity. More efficient and practical iterative strategies are anticipated to emerge in the future development.

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“…Starting with 1-cyanovinyl (1 S ) -camphanate leads to the diastereoisomeric adduct (-)-3 and enantiomeric enone (-)-2 with the same ease ('naked sugars of the second generation' [20]). The Diels-Alder approach to the synthesis of polypropionates had been applied earlier by Danishefsky and coworkers [21] to prepare a racemic precursor of 6-deoxyerytrothonolide B. Recently, Yamanzoto and coworkers [22] have shown that the hetero-Diels-Alder additions of furan-2-carboxaldehyde to (E)-1 -methoxy-2-methyl-3-(trimethylsilyloxy)penta-1,3-diene used by Danishefsky [21] can now be carried out with excellent asymmetric induction with a homochiral Lewis-acid catalyst.…”

Section: (2rs3rs4sr5sr6sr7~s)-7-(3'5'-dimethylfuran-2-yl)-2-ethmentioning

confidence: 99%

“…The Diels-Alder approach to the synthesis of polypropionates had been applied earlier by Danishefsky and coworkers [21] to prepare a racemic precursor of 6-deoxyerytrothonolide B. Recently, Yamanzoto and coworkers [22] have shown that the hetero-Diels-Alder additions of furan-2-carboxaldehyde to (E)-1 -methoxy-2-methyl-3-(trimethylsilyloxy)penta-1,3-diene used by Danishefsky [21] can now be carried out with excellent asymmetric induction with a homochiral Lewis-acid catalyst. The bicyclic alkenes (+)-1, (+)-2, (-)-3, and (-)-2 have been converted into all kinds of polypropionate fragments [19] [20] [23] [24] including long-chain derivatives containing up to eleven contiguous stereogenic centres and tertiary-alcohol moieties [2].…”

Section: (2rs3rs4sr5sr6sr7~s)-7-(3'5'-dimethylfuran-2-yl)-2-ethmentioning

confidence: 99%

A New Approach to the Synthesis of Long‐Chain Polypropionates Based on the Diels‐Alder Monoadditions of 2,2′‐Ethylidenebis[3,5‐dimethylfuran]

Ancerewicz

Vogel

1996

Helvetica Chimica Acta

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Acidic condensation of 2,4-dimethylfuran with acetaldehyde provided 2,2-ethylidenebis[3,5-dimethylfuran] (7) which added 1 equiv. of methyl bromopropynoate to give a major adduct 8. Regio-and stereoselective hydroboration of the latter 7-oxanorbornadiene derivative followed by alcohol protection and methanolysis of its P-bromoacrylate moiety gave (1 RS,2RS,4RS,SSR,6SR, 1'RS)-methyl 4-[l'-(3",5"-dirnethylfuran-2"-yl)ethyl]-3,3-dimethoxy-6-exo -[(2-methoxy)ethoxy]-1,5-endo-dimethyl-7-oxabicyclo[2.2.l]heptane-2-endo -carboxylate (24) (Schemes 2 and 3). Reduction of 24 with LiAIH,, followed by H,O and MeOH elimination gave the 3-methylidene-7-oxanorbornan-2-one derivative 26 which underwent 7-oxa ring opening through a SJ' type of reaction with Me2CuLi (Scheme 4). Stereoselective hydrogenation and ketone reduction provided (1RS,2SR,3RS,4RS, [2]). In 1956, Woodward [3] described these compounds as 'hopelessly complex' for synthesis. Since then, several methods and strategies have been developed to provide access to these systems which possess a large number of stereogenic centres [4] (see also ref. 4-16 in [21). During the seventies and eighties, the carbohydrate approach was the most popular to construct these acyclic chains. More recently, the advent of new chiral auxiliaries [5] and chirons [6], as well as the development of new techniques to control the diastereoselectivity of aldehyde nucleophilic additions [7] and cross-aldolization [8], made possible the total, asymmetric synthesis of a large number of polypropionate natural products and analogues [9]. Other approaches imply two-directional chain elongation and a 'desymmetrization' process [ 101. Bicyclic alkenes and ketones that display high facial selectivity in their reactions for steric reasons have also been used as starting materials [ll-181. We have shown [19] that the Zn1,-catalyzed Diels-Alder addition of 2,4-dimethylfuran to 1 -cyanovinyl (1R)-camphanate leads to optically pure adduct (+)-1 in high yield, the saponification of which furnishes enone (+)-2 and allows one

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Development of a fully synthetic stereoselective route to 6-deoxyerythronolide B by reiterative applications of the Lewis acid catalyzed diene aldehyde cyclocondensation reaction: a remarkable instance of diastereofacial selectivity

Cited by 62 publications

References 0 publications

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

Bioinspired iterative synthesis of polyketides

A New Approach to the Synthesis of Long‐Chain Polypropionates Based on the Diels‐Alder Monoadditions of 2,2′‐Ethylidenebis[3,5‐dimethylfuran]

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